King's College London

The arrival of cell-based therapies is a revolution in medicine. However, its safe clinical application in a rational manner depends on reliable, clinically applicable methods for determining the fate and trafficking of therapeutic cells in vivo using medical imaging techniques – known as in vivo cell tracking. Radionuclide imaging using single photon emission computed tomography (SPECT) or positron emission tomography (PET) has several advantages over other imaging modalities for cell tracking due to its high sensitivity (requiring low amounts of probe per cell for imaging) and wholebody quantitative imaging capability using clinically available scanners. For cell tracking with radionuclides, ex vivo direct cell radiolabelling, i.e. radiolabelling cells before their administration, is the simplest and most robust method, allowing labelling of any cell type without the need for genetic modification. This review covers the development and application of direct cell radiolabelling probes
utilising a variety of chemical approaches: organic and inorganic/coordination (radio)chemistry, nanomaterials, and biochemistry. We describe the key early developments and the most recent advances in the field, identifying advantages and disadvantages of the different approaches and informing future development and choice of methods for clinical and pre-clinical application.